The [alpha]10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system

Although homomeric channels assembled from the [alpha]9 nicotinic acetylcholine receptor (nAChR) subunit are functional in vitro, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both [alpha]9 and [alpha]10 subunits. To gain insight into [alpha]10 subunit function in vivo, we examined olivocochlear innervation and function in [alpha]10 null-mutant mice. Electrophysiological recordings from postnatal (P) days P8-9 inner hair cells revealed ACh-gated currents in [alpha][10.sup.+/+] and [alpha][10.sup.+/-] mice, with no detectable responses to ACh in [alpha][10.sup.-/-] mice. In contrast, a proportion of [alpha][10.sup.-/-] outer hair cells showed small ACh-evoked currents. In [alpha][10.sup.-/-] mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual [alpha]9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals in vivo. Finally, [alpha][10.sup.-/-] mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that [alpha][9.sup.-/-] and [alpha][10.sup.-/-] mice have overlapping but nonidentical phenotypes. Moreover, [alpha]10 nAChR subunits are required for normal olivocochlear activity because [alpha]9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in [alpha][10.sup.-/-] mutant mice. cochlea | electrophysiology | inner hair cells | outer hair cells